The number of genes implicated in alcohol dependence and other psychiatric illnesses continues to grow, with no single factor being uniquely responsible for the genotype–phenotype relationship. This is not a surprising notion, given that genes and their ensuing proteins do not exist in isolation, but work through coordinated pathways to govern cellular actions. Current canonical pathways, although useful to some extent, are becoming increasingly inadequate to account for the multitude of factors driving cellular behavior and manifesting phenotypes (Califano, Butte, Friend, Ideker, & Schadt, 2012). Using a variety of high-throughput approaches, both expected and unexpected connections can be simultaneously established among multiple cellular substrates to define biological networks for nearly any condition (Barabási & Oltvai, 2004; Vidal, Cusick, & Barabási, 2011). Not all genetic perturbations may be of equal value but may spread their effects across a web of neighboring genes to propagate disease symptomology. Disease-associated genes form an extended network that surrounds highly connected hub genes, which are essential to influence multiple biochemical pathways for development and survival (Goh et al., 2007). Understanding phenotypes across a spectrum of human disorders will require understanding the corresponding network architecture of related diseases.
